Inhibition of human non-small cell lung cancers with a targeted cytotoxic somatostatin analog, AN-162

Andrea Treszl, Andrew V. Schally, Stephan Seitz, Luca Szalontay, Ferenc G. Rick, Karoly Szepeshazi, Gabor Halmos

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Human non-small cell lung cancers (NSCLCs) express receptors for somatostatin. The cytotoxic analog of somatostatin AN-162 (AEZS-124), consisting of doxorubicin linked to a somatostatin analog RC-121 binds to receptors for somatostatin and is targeted to tumors expressing these receptors. The aim of this study was to investigate the effect of targeted cytotoxic somatostatin analog AN-162 on a panel of human NSCLC cell lines (A549, H460, H838, H1299) in vitro (at 0.5-100 μM concentrations) and in vivo on H460 and H1299 NSCLCs xenografted into nude mice (at the dose of 2.5 μmol/kg, i.v., once a week). The expression of mRNA for somatostatin receptor subtypes was investigated by RT-PCR in cell lines and tumor tissues. Somatostatin receptor proteins were also characterized by ligand competition assay and Western blotting. AN-162 significantly decreased cell proliferation in vitro and tumor growth (p < 0.05 vs. all groups) of H460 and H1299 NSCLCs in vivo. Based on real-time PCR array data, AN-162 induced several apoptosis-related genes in vivo in both models. Our results suggest that cytotoxic somatostatin analog AN-162 (AEZS-124) should be considered for the further development of a therapy of patients with NSCLC.

Original languageEnglish (US)
Pages (from-to)1643-1650
Number of pages8
JournalPeptides
Volume30
Issue number9
DOIs
StatePublished - Sep 1 2009

Keywords

  • Cytotoxic somatostatin analog AN-162
  • H1299 xenograft
  • H460 xenograft
  • Non-small cell lung cancer
  • Somatostatin receptors

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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